グルタミン酸神経毒性と神経保護因子

概要

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Glutamate is acknowledged as an excitatory neurotransmitter in the vertebrate central nervous system (CNS). Glutamate is also postulated to play an important role in the pathogenesis of the neuronal cell loss that is associated with several neurological disease states in the CNS. Glutamate cytotoxicity in the cortical and retinal neurons in culture is mediated by nitric oxide (NO). As the excitatory action of glutamate is regulated by other neurotransmitters, the cytotoxic action of glutamate may be affected by other endogenous substances. We have used the term “neuroprotective factor” for endogenous substances having neuroprotective actions against glutamate cytotoxicity. We have previously found that cholecystokinin (CCK) prevented glutamate toxicity in the cortical neurons in culture. The evidence has suggested that CCKB-receptor stimulation causes suppression of a step in NO formation triggered by N-methyl-D-aspartate (NMDA) receptors. Nicotinic acetylcholine also protected cultured cortical neurons against NMDA receptor-mediated glutamate toxicity. In the cultured retinal neurons, dopamine prevented NMDA receptor-mediated glutamate cytotoxicity via D1-receptors. These substances may have a role to promote cell survival in the life-regulatory function of the CNS.
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